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DOI: 10.1055/s-2006-943409
The behaviour of matrix metalloproteinase-9, hepatocyte growth factor receptor and insulin-like growth factor receptor-I expressions in ulcerative colitis
Background: Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease. Matrix metalloproteinases play an important part in extracellular matrix remodelling. Hepatocyte growth factor receptor (c-met) and insulin-like growth factor receptor-I (IGFR-1) modulate intestinal epithelial cell proliferation and migration, play a role in regenerative processes and intestinal wound healing.
Aim: Determination of protein expression levels and mRNA of matrix metalloproteinase-9 (MMP-9), c-met and IGFR-1 in correlation with the severity of inflammation in ulcerative colitis (UC).
Materials and methods: MMP-9, c-met and IGFR expressions were analyzed in 40 paraffin-embedded tissue samples by immunohistochemistry from patients with mild (n=10), moderate (n=10), severe (n=10) UC and healthy control subjects (n=10). Immunostaining was determined semiquantitatively. The RNA expression profile from biopsy samples was evaluated using TaqMan® assay Low-Density Array to Gene Expression (Applied Biosystems). Statistical analysis with one-way ANOVA and LSD tests were performed.
Results: MMP-9 expression was significantly lower in each inflammatory group compared with normal (p<0.05). IGFR-1 and c-met expressions were significantly higher in mild UC, but not in moderate and severe UC compared to normal (p<0.005). MMP-9 and IGFR-1 mRNA expressions were significantly down-regulated in UC compared to the normal tissue (p<0.05), while c-met mRNA expression was slightly, but not significantly higher only in mild UC compared to normal. The immunohistochemical protein expression levels correlated to the mRNA expression array data.
Conclusions: The down-regulation of MMP-9, IGFR-1 and c-met expression correlated with the severity of inflammatory process in UC. The decrease of MMP-9 expression with the decreased IGFR-1 and c-met expressions could contribute to the severity of epithelial damage in moderately and severely active UC.